One-stage implant in sacral neuromodulation for faecal incontinence - short-term outcome from a prospective study.

AIM: Sacral neuromodulation (SNM) is approved for the treatment of faecal incontinence (FI) in a two-stage technique. With standardized implantation, approximately 90% of patients undergo successful Stage I operation and proceed to a permanent implant (Stage II). The aim of this work was to explore the feasibility of SNM as a one-stage procedure and report the 24-week efficacy. METHOD: This study included patients diagnosed with idiopathic FI or FI due to an external anal sphincter defect ≤160° and one or more episodes of FI per week despite maximal conservative therapy. Patients were offered a one-stage procedure if a motor response of the external anal sphincter was achieved in three or more poles with at least one at ≤1.5 mA at lead placement. Patients were followed for 24 weeks. Their evaluation included the Wexner/St Mark's Incontinence Score, Faecal Incontinence Quality of Life score (FIQoL), a visual analogue scale (VAS) for assessing patient satisfaction and a bowel habit diary. RESULTS: Seventy-three patients with a median age of 60 years (interquartile range 50-69 years) completed this prospective study. Episodes of FI were significantly reduced at the 24-week follow-up, from 13 (8-23) at baseline to 2 (0-5) (p-value = 0002). A ≥50% reduction in the number of FI episodes was achieved in 92% of participants. The Wexner score improved significantly from 16 (14-17) at baseline to 9 (5-13) (p-value < 0.001), and the St Mark's score improved significantly from 18 (16-20) to 11 (7-16) (p-value < 0.001). All domains in the FIQoL score and VAS for patient satisfaction improved significantly following the one-stage procedure. CONCLUSION: A one-stage implantation procedure is feasible in selected patients with FI, significantly improving continence, quality of life and patient satisfaction after 24 weeks of follow-up.

A European snapshot of psychosocial characteristics and patients' perspectives of faecal incontinence-do they correlate with current scoring systems?

PURPOSE: To compare the current clinical scoring systems used to quantify the severity of symptoms of faecal incontinence (FI) to patients' subjective scoring of parameters of psychosocial well-being. METHODS: Patients referred to six European centres for investigation or treatment of symptoms of FI between June 2017 and September 2019 completed a questionnaire that captured patient demographics, incontinence symptoms using St. Mark's Incontinence score (SMIS) and ICIQ-B, psychological well-being (HADS, Hospital Anxiety and Depression Scale), and social interaction (a three-item loneliness scale). RESULTS: Three hundred eighteen patients completed questionnaires (62 men, mean age 58.7). Sixty percent of the respondents were aged under 65. Median SMIS was 15 (11-18), ICIQ-B bowel pattern was 8 (6-11) and bowel control was 17 (13-22), similar across all demographic groups; however, younger patients were more likely to experience symptoms of depression and anxiety (HADS score > 10, 65.2% of patients age < 65 vs 54.9% of those ages > = 65, p = 0.03) with lower quality of life (ICIQ-B QoL, median score 19 (14-23)) vs age > = 65 (16 (11-21) (p < 0.005)). On loneliness score 25.5% reported often feeling isolated from others. One of the most significant concerns by patients was the fear and embarrassment related to unpredictable episodes of incontinence. CONCLUSION: The SMIS remains a useful tool for quantifying incontinence symptoms but may underestimate the psychosocial morbidity associated with unpredictable episodes of incontinence. Interventions aimed at decreasing anxiety and to address feelings of disgust may be helpful for a significant number of patients requiring treatment for FI.

Long-term Experience of Magnetic Anal Sphincter Augmentation in Patients With Fecal Incontinence.

BACKGROUND: Magnetic anal sphincter augmentation is a novel technique for the treatment of patients with fecal incontinence. OBJECTIVE: The current study reports the long-term effectiveness and safety of this new treatment modality. DESIGN: This was a prospective multicenter pilot study. SETTINGS: The study was performed at 4 clinical sites in Europe and the United States. PATIENTS: The cohort included patients with severe fecal incontinence for ≥6 months who had previously failed conservative therapy and were implanted with a magnetic anal sphincter device between 2008 and 2011. MAIN OUTCOME MEASURES: Adverse events, symptom severity, quality of life, and bowel diary data were collected. RESULTS: A total of 35 patients (34 women) underwent magnetic anal sphincter augmentation. The median length of follow-up was 5.0 years (range, 0-5.6 years), with 23 patients completing assessment at 5 years. Eight patients underwent a subsequent operation (7 device explantations) because of device failure or complications, 7 of which occurred in the first year. Therapeutic success rates, with patients who underwent device explantation or stoma creation counted as treatment failures, were 63% at year 1, 66% at year 3 and 53% at year 5. In patients who retained their device, the number of incontinent episodes per week and Cleveland Clinic incontinence scores significantly decreased from baseline, and there were significant improvements in all 4 scales of the Fecal Incontinence Quality of Life instrument. There were 30 adverse events reported in 20 patients, most commonly defecatory dysfunction (20%), pain (14%), erosion (11%), and infection (11%). LIMITATIONS: This study does not allow for comparison between surgical treatments and involves a limited number of patients. CONCLUSIONS: Magnetic anal sphincter augmentation provided excellent outcomes in patients who retained a functioning device at long-term follow-up. Protocols to reduce early complications will be important to improve overall results.

Sacral nerve stimulation for faecal incontinence - efficacy confirmed from a two-centre prospectively maintained database.

INTRODUCTION: Sacral nerve stimulation (SNS) has been recognised as an effective treatment for faecal incontinence. Many unresolved questions could be answered when comparing large data-series from different centres providing prospective data. AIM: To present data, from an international two-centre SNS prospective database (SNSPD) on functional outcome and management of surgical complications in patients treated with SNS for faecal incontinence. METHOD: The SNSPD was designed in order to gather detailed pre- and perioperative information followed by a close follow-up in all patients undergoing SNS for bowel dysfunction. The SNSPD was open for inclusion of newly SNS implanted patients in May 2009, and closed on 31 December 2013. Two-centres Aarhus, Denmark, and Nantes, France, included and monitored all patients implanted due to bowel dysfunction according to database criteria. RESULTS: In total, 164 faecal incontinent patients with a median follow-up of 22 (range 1-50) months were implanted. The Wexner incontinence score improved from 15 (range, 3-20) at baseline to 9 (range, 0-20) at latest follow-up (P < 0.001) and VAS impact on daily life improved from 85.5 (range, 3-100) to 20 (range, 0-100) (P < 0.001). Additional surgical intervention was required in 19.5 % during follow-up. Repositioning of the pacemaker due to pain or migration was the most common complication in 12.1 %. Infections leading to explantation occurred in 3.0 %.

Outcome of sacral nerve stimulation for fecal incontinence at 5 years.

OBJECTIVE: This study aimed to evaluate the outcome of sacral nerve stimulation (SNS) for fecal incontinence at 5 years after implantation and to identify predictors of sustained efficacy. BACKGROUND: There is a lack of knowledge about the long-term outcome of SNS for fecal incontinence. METHODS: Prospectively collected data from patients who underwent implantation of an SNS device between 2001 and 2006 were reviewed. RESULTS: One hundred and one patients were available for outcome evaluation at 5 years. Sixty of 101 patients [42.6% on intention-to-treat (ITT) and 55.6% per protocol (PP)] reported a favorable outcome, 41 patients (ITT 29.1%; PP 38.0%) reported an unfavorable outcome, of whom 24 patients (ITT 17.0%; PP 22.2%) had their device explanted or permanently switched off before 5 years. Wexner incontinence scores improved significantly from a baseline median of 16 (range 6-20) to a median of 6 (range 0-20) at 3 months (P < 0.0001), and the improvement compared with baseline was maintained throughout the 5-year follow-ups (P < 0.0001).Age was a negative predictive factor [odds ratio (OR): 0.96 each year increase, 95% confidence interval (CI): 0.92-0.99; P = 0.016]. Positive predictors included improvement of urge incontinence episodes during percutaneous nerve evaluation (OR: 10.8; 95% CI: 1.72-132; P = 0.036), improvement of incontinence scores at 6 months from baseline (OR: 6.29; 95% CI: 1.33-34.3; P = 0.025), particularly improvement of incontinence scores from 3 to 6 months (OR: 41.5; 95% CI: 3.51-811; P = 0.007). Overall, 521 reportable events were recorded from 94 patients (93.1%). CONCLUSIONS: On an ITT analysis, 42.6% of patients reported favorable outcomes at 60 months. Patient's age, improvement of urge incontinence during PNE, and sustained efficacy during the first 6 months after implantation are some of the predictors identified.

A randomized, controlled, crossover study of sacral nerve stimulation for irritable bowel syndrome.

OBJECTIVE: To investigate whether sacral nerve stimulation reduces irritable bowel syndrome (IBS)-specific symptoms by a randomized, controlled, crossover study. BACKGROUND: IBS affects 3% to 22% of the population worldwide, but most patients continue to have symptoms despite treatment. METHODS: Patients included from our tertiary center had diarrhea-predominant or mixed IBS, with a minimum baseline IBS symptom score (Gastrointestinal Syndrome Rating Scale-IBS questionnaire) of 40 points reduced by a minimum of 30% during the percutaneous nerve evaluation before permanent implantation. Patients were randomized (1:1) to have the stimulator ON or OFF for 1 month and then the opposite for another month. Investigators and patients were not informed of the setting. IBS-specific symptoms and quality of life were assessed through bowel diaries and validated questionnaires. Primary endpoint was the IBS-specific symptom score. RESULTS: Twenty-one patients were randomized. Ten were eligible for analysis in each group. IBS-specific symptom scores were significantly reduced during stimulation: the median difference in the ON-OFF group was 12 (range, -22 to 44) and in the OFF-ON group -17.5 (range, -48 to -1) (P = 0.0009). IBS-specific quality-of-life scores improved significantly during stimulation: the median difference in the ON-OFF group was 16 (range, -24 to 69) and in the OFF-ON group -42.5 (range, -77 to 0) (P = 0.0003). At 1-year follow-up, the median IBS-specific symptom score (25; range, 13-65) was significantly lower than that at baseline (62; range, 45-80) (P = 0.0001). CONCLUSIONS: Sacral nerve stimulation significantly reduces symptoms and improves quality of life of highly selected patients with IBS.

A randomised, controlled study of small intestinal motility in patients treated with sacral nerve stimulation for irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is among the most common gastrointestinal disorders worldwide. In selected patients with severe diarrhoea-predominant or mixed IBS subtypes sacral nerve stimulation (SNS) alleviates IBS-specific symptoms and improves quality of life. The mode of action, however, remains unknown. The present study aimed to evaluate the effect of SNS on small intestinal motility in IBS patients. METHODS: Twenty patients treated with SNS for severe diarrhoea-predominant or mixed IBS were included in a randomised, controlled, crossover study. The neurostimulator was turned ON or OFF for the first one month and then to the opposite setting for the next month. Gastrointestinal transit patterns were investigated with the Motility Tracking System-1 (MTS-1) at the end of each the ON and OFF period. Primary endpoint was change in the velocity of the magnetic pill within the small intestine. Statistical testing was performed with Wilcoxon's rank sum test and Fisher's exact test. RESULTS: The median velocity of the magnetic pill through the small intestine in the fasting state was not significantly different between periods with and without SNS (Group ON-OFF: median change 0 m/h (range -1.07, 0.63), Group OFF-ON: median change 0.27 m/h (range -0.59, 1.12)) (p = 0.25). Neither, was the median velocity of the magnetic pill through the small intestine in the postprandial state significantly different between periods with and without SNS (Group ON-OFF: median change -0.13 m/h (range -0.46, 0.23), Group OFF-ON: median change 0.015 m/h (range -0.48, 0.59)) (p = 0.14). CONCLUSION: Even though SNS may reduce symptoms of diarrhoea-predominant and mixed IBS, it has no detectable effect on small intestinal transit patterns. TRIAL REGISTRATION: Clinical.trials.gov, (NCT00919672).

Baseline factors predictive of patient satisfaction with sacral neuromodulation for idiopathic fecal incontinence.

PURPOSE: Sacral neuromodulation (SNM) is an established treatment for fecal incontinence (FI). A recent study from our group found that the relationship between patient satisfaction and clinical outcome is complex and does not match the traditional used success criteria. Therefore, the ability to predict patient satisfaction must be given priority. The aim of the present study is to identify baseline factors predictive of patient satisfaction, with SNM, for idiopathic FI. METHODS: We analyzed data from patients treated with SNM for idiopathic FI in Aarhus, Denmark, and Maastricht, The Netherlands. A questionnaire considering self-reported satisfaction was mailed to these patients and compared to baseline characteristics. Logistic regression was used to determine the predictive value of baseline demographic and diagnostic variables. RESULTS: In total, 131 patients were included in the analysis. Patient satisfaction with the current treatment result was reported in 75 patients. Fifty-six patients were dissatisfied with SNM treatment, after median 46 months (range 11-122) with permanent implantation. Pudendal nerve terminal motor latency (PNTML) was the solely identified predictor for long-term patient satisfaction. A subgroup univariate-logistic regression analysis showed that PNTML ≤ 2.3 ms at the side of lead implantation was a statistically significant predictor for patient satisfaction (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.01-5.24, p = 0.048). CONCLUSION: Baseline PNTML measurement may be predictive of long-term satisfaction with SNM therapy for idiopathic FI. Further studies are needed to confirm this result.

Sacral nerve stimulation at subsensory threshold does not compromise treatment efficacy: results from a randomized, blinded crossover study.

BACKGROUND AND OBJECTIVE: : Stimulation amplitude used in sacral nerve stimulation (SNS) is at or just above the sensory threshold (ST). This randomized, blinded crossover study aimed to document if stimulation at 75% or 50% of the ST would be as effective as stimulation at the ST for fecal incontinence (FI). METHOD: : FI patients treated with SNS, who were satisfied with current treatment results and had a minimum symptom reduction of 75%, were eligible. Patients were randomized into 3 periods of 4-week stimulation: ST, 75% of the ST, and 50% of the ST. Patients completed a bowel habit diary and questionnaires on bowel functions and patient satisfaction at the study baseline and in each study period. RESULTS: : Nineteen patients (18 females) with a mean follow-up of 51.7 ± 29.9 months were included from January to April 2010. The mean FI episodes per 3 weeks decreased from pre-SNS therapy 33.6 ± 31.6 to 1.1 ± 2.2 at the study baseline (P < 0.001). Decreasing the stimulation amplitude to as low as 50% of the ST did not affect the overall number of incontinent episodes (P = 0.078). The Wexner incontinence score dropped from 16.5 ± 2.5 for pre-SNS therapy to 7.4 ± 3.1 at the study baseline (P < 0.001). Decreasing the stimulation amplitude to ST, 75% of the ST or 50% of the ST, did not change the Wexner score when compared with the study baseline (P = 0.581). In general, patient satisfaction was high at the study baseline and did not deteriorate as the stimulation amplitude was decreased to 50% of the ST (P = 0.932). CONCLUSIONS: : Subsensory stimulation as low as 50% of the ST is as effective as stimulation at or above the ST. The study was approved by the Regional Committee on Biomedical Research Ethics, Denmark, and registered at ClinicalTrials.gov (NCT01130870).

Complete obstetric anal sphincter tear and risk of long-term fecal incontinence: a cohort study.

BACKGROUND: Women with anal sphincter injuries have an increased risk of developing fecal incontinence despite surgical intervention. OBJECTIVE: The aim of this study was to evaluate the long-term risk of fecal incontinence after primary anal sphincter reconstruction and its impact on quality of life. DESIGN: This was a cohort study. SETTINGS: This study was performed at Aarhus University Hospital. PATIENTS: Women with complete anal sphincter rupture (exposed) from 1976 to 1991 and a control group of parous women (nonexposed) were included. MAIN OUTCOME: The primary outcomes measured were fecal incontinence, Wexner score, St Mark incontinence score, and quality of life. RESULTS: A total of 363 women were included (125 exposed and 238 nonexposed). The mean age was 50.4 years (95%CI: 49.8-51.0), with 22.2 years (95% CI: 21.7-22.6) of follow-up. At the time of follow-up, 49% of exposed women and 74% of nonexposed women were continent. Complete anal sphincter tear increases the risk of fecal incontinence twofold (relative risk = 2.00; 95%CI: 1.52-2.63). No other risk factors were identified. The mean Wexner score was 1.7 (95%CI: 1.3-2.1) vs 1.1 (95%CI: 0.7-1.4) (p = 0.02), and the mean St Mark score was 2.8 (95% CI: 2.1-3.4) vs 1.4 (95%CI: 1.0-1.9) (p < 0.001) in the exposed and nonexposed groups. Severity of fecal incontinence had a significant impact on the quality of life independent of exposure. LIMITATION: The cohort is relatively young; a short postmenopausal period limits the assessment of hormonal status and the effect of postmenopausal hormone replacement therapy. CONCLUSION: Complete obstetric anal sphincter tear increases the long-term risk of fecal incontinence twofold. When present, the severity of the incontinence symptoms is minor and the risk of incontinence for solid stool is not increased in comparison with the general population. Anal sphincter rupture is the only independent risk factor for fecal incontinence. The severity of fecal incontinence had the same impact on quality of life in both groups.

Medium-term outcome of sacral nerve modulation for constipation.

BACKGROUND: Sacral nerve modulation has been reported as a minimally invasive and effective treatment for constipation refractory to conservative treatment. OBJECTIVE: This study aimed to evaluate the efficacy and sustainability of sacral nerve modulation for constipation in the medium term (up to 6 years) and to investigate potential predictors of treatment success. DESIGN: We performed a retrospective review of prospectively collected data. SETTINGS: The study was performed at 2 tertiary-care centers in Europe with expertise in pelvic floor disorders and sacral nerve modulation. PATIENTS: Patients were eligible if they had had symptoms of constipation persisting for at least 1 year, if conservative treatment (dietary modification, laxatives and biofeedback therapy) had failed, and if predefined excluded conditions were not present. INTERVENTION: The first phase of the treatment process was percutaneous nerve evaluation. If this was successful, patients underwent sacral nerve modulation therapy with an implanted device (tined-lead and implantable pulse generator). MAIN OUTCOME MEASURE: Follow-up was performed at 1, 3, 6, and 12 months, and yearly thereafter. Outcome was assessed with the Wexner constipation score. RESULTS: A total of 117 patients (13 men, 104 women) with a mean age of 45.6 (SD, 13.0) years underwent percutaneous nerve evaluation. Of these, 68 patients (58%) had successful percutaneous nerve evaluation and underwent implantation of a device. The mean Wexner score was 17.0 (SD, 3.8) at baseline and 10.2 (SD 5.3) after percutaneous nerve evaluation (p < .001); the improvement was maintained throughout the follow-up period, although the number of patients continuing with sacral nerve modulation at the latest follow-up (median, 37 months; range, 4-92) was only 61 (52% of all patients who underwent percutaneous nerve evaluation). The sole predictive factor of outcome of percutaneous nerve evaluation was age: younger patients were more likely than older patients to have a successful percutaneous nerve evaluation phase. LIMITATIONS: The study was limited by a lack of consistent outcome measures. CONCLUSIONS: : Despite improvement in Wexner scores, at the latest follow-up sacral nerve modulation was only being used by slightly more than 50% of the patients who started the first phase of treatment. Further studies are needed to reassess the efficacy and sustainability of sacral nerve modulation.

Postoperative issues of sacral nerve stimulation for fecal incontinence and constipation: a systematic literature review and treatment guideline.

BACKGROUND: There is a lack of knowledge on the incidence and management of suboptimal therapeutic effect and the complications associated with sacral nerve stimulation for fecal incontinence and constipation. OBJECTIVE: This study aimed to review current literature on postoperative issues and to propose a treatment algorithm. DATA SOURCE: PubMed, MEDLINE, and EMBASE were searched using the keywords "sacral nerve stimulation," "sacral neuromodulation," "fecal incontinence," and "constipation" for English-language articles published from January 1980 to August 2010. A further search was conducted on a wider literature using the keywords "complication," "adverse effect," "treatment failure," "equipment failure," "infection," "foreign-body migration," "reoperation," "pain," and "algorithm." STUDY SELECTION: Four hundred sixty-one titles were identified, and after a title and abstract review, 135 were subjected to full article review; 89 were finally included in this review. Five articles were added by manual search and consensus. RESULTS: Forty-eight studies were identified as cohort studies reporting on postoperative issues, including 1661 patients who underwent percutaneous nerve evaluation and 1600 patients who proceeded to sacral nerve stimulation therapy. Pooled data showed that the most common problem during percutaneous nerve evaluation was lead displacement (5.3%). The incidence of suboptimal outcome, pain, and infection after implantation was 12.1%, 13.0%, and 3.9%. LIMITATIONS: There was significant underreporting of untoward events, because 60% of the studies did not report complications during percutaneous nerve evaluation, and suboptimal outcome after implantation was not disclosed in 44% of the studies. CONCLUSIONS: The incidence of untoward events associated with sacral nerve stimulation appears to be low. However, there is a significant underreporting of the incidence. Using the information from the structured and systematic literature review, we formulated a clinically relevant guideline for reporting and managing postoperative issues. The guideline can provide a framework for clinical practice.

Relief of fecal incontinence by sacral nerve stimulation linked to focal brain activation.

OBJECTIVE: This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence. PATIENTS: Nine women and one man received temporary sacral nerve stimulation with permanent electrodes as a treatment for fecal incontinence. INTERVENTIONS: We used positron emission tomography to record indices of regional cerebral blood flow before and after 30 minutes of continuous stimulation. We repeated this procedure after 2 weeks of continued stimulation, before and 30 minutes after arrest of the stimulation. RESULTS: The initial stimulation activated a region of the contralateral frontal cortex that normally is active during focused attention. After 2 weeks of stimulation, this activation had been replaced by activity in parts of the ipsilateral caudate nucleus, a region of the brain thought to be specifically involved in learning and reward processing. CONCLUSIONS: Sacral nerve stimulation induces changes in cerebral activity consistent with an effect on afferent projections of the vagus. The initial activation of the frontal cortex may reflect focused attention, whereas the subsequent activation of the caudate nucleus may reflect recruitment of mechanisms involved in learning and reward processing. These changes may contribute to the improved continence, which is an acquired result of the stimulation.

Sacral nerve stimulation for intractable constipation.

OBJECTIVE: Traditional surgical procedures for intractable idiopathic constipation are associated with a variable outcome and substantial morbidity. The symptomatic response, physiological effect and effect on quality of life of sacral nerve stimulation (SNS) were evaluated in patients with constipation (slow transit and normal transit with impaired evacuation). METHODS: In a prospective study at five European sites patients who failed conservative treatment underwent 21 days test stimulation. Patients with >50% improvement in symptoms underwent permanent neurostimulator implantation. Primary end points were increased defecation frequency, decreased straining and decreased sensation of incomplete evacuation. RESULTS: 62 patients (55 female, median age 40 years) underwent test stimulation, of whom 45 (73%) proceeded to chronic stimulation. 39 (87%) of these 45 patients achieved treatment success. After a median 28 (range 1-55) months follow-up, defecation frequency increased from 2.3 to 6.6 evacuations per week (p<0.001). Days per week with evacuation increased from 2.3 to 4.8 (p<0.001). There was a decrease in time spent toileting (10.5 to 5.7 min, p=0.001), straining (75-46% of successful evacuations, p<0.001), perception of incomplete evacuation (71.5-46% of successful evacuations, p<0.001) and subjective rating of abdominal pain and bloating (p<0.001). Cleveland Clinic constipation score (0=no to 30=severe constipation) decreased from 18 to 10 (p<0.001). Visual analogue scale (VAS) score (0=severe to 100=no symptoms) increased from 8 to 66 (p<0.001). Patients with slow and normal transit benefited. Quality of life significantly improved. Colonic transit normalised in half of those with baseline slow transit (p=0.014). CONCLUSION: SNS is effective in the treatment of idiopathic slow and normal transit constipation resistant to conservative treatment. Clinical Trial Number NCT00200005.

Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas.

BACKGROUND: Injection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process. METHODS: 27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing. RESULTS: 52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1. CONCLUSION: Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome. TRIAL REGISTRATION: NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609.

Sacral nerve stimulation for constipation: suboptimal outcome and adverse events.

PURPOSE: Sacral nerve stimulation is an emerging treatment for patients with severe constipation. There has been no substantial report to date on suboptimal outcomes and complications. We report our experience of more than 6 years by focusing on incidents and the management of reportable events. METHODS: A retrospective review was performed on patients who underwent sacral nerve stimulation for constipation between August 2002 and September 2008. Collected data included patients' demographic data, type and management of suboptimal outcomes and complications, and stimulation parameters at the time of reportable events. RESULTS: Thirty-eight patients (32 women; mean age, 45.6 y; SD, 11.8; range, 21-66) received a permanent stimulator after a successful test period. The mean treatment duration was 25.7 months (SD, 20.4; range, 0-70). Twenty-two patients (58%) experienced at least one reportable event attributable to the treatment. The total of 58 reportable events were noted, including lack or loss of efficacy, pain, and undesired change of sensation. Reprogramming successfully managed 28 reportable events (48%), 19 events (33%) required surgical interventions, and 3 adverse events led to discontinuation of the treatment. CONCLUSIONS: Nearly 60% of patients who received sacral nerve stimulation for constipation experienced at least one reportable event. Although the events were often resolved by reprogramming, more than one-third required surgical intervention or discontinuation of therapy. Patients undergoing sacral nerve stimulation for constipation need to be informed of these possibilities. A systematic assessment is needed to identify the cause and optimize the management of reportable events.

Six years of experience with sacral nerve stimulation for fecal incontinence.

PURPOSE: Sacral nerve stimulation is one of many new surgical modalities for fecal incontinence. Short-term results from sacral nerve stimulation have been more encouraging than those from other modalities. The aim of this study was to report the outcome of percutaneous nerve evaluation tests and sacral nerve stimulation for the treatment of fecal incontinence from a single center covering a period of 6 years since the procedure was introduced. METHODS: All of the candidates for a percutaneous nerve evaluation test and sacral nerve stimulation seen at our anal physiology unit between March 2001 and March 2007 were included in the study. RESULTS: A total of 177 patients with fecal incontinence (160 females), median age 59.5 (range, 27-88) years, underwent a percutaneous nerve evaluation test. Of these patients, 142 (80%) had a positive test, including 21 of 25 (84%) patients who required a repeat percutaneous nerve evaluation test. Because of a functional failure, 16 patients underwent a revision of the permanent electrode, 7 of whom (44%) were satisfied with the functional result after the revision. Of 126 patients, 15 (12%) have undergone an explantation, with an infection rate of only 1.6%. Overall, after a median follow-up of 24 (range, 3-72) months, the median Wexner incontinence score decreased from 16 (range, 6-20) to 10 (range, 0-20) (P < .0001). In the 10 patients who underwent at least 6 years of treatment, the effect was sustained, as the median Wexner incontinence score decreased from 20 (range, 12-20) to 7 (range, 2-11) (P < .0001). CONCLUSION: Sacral nerve stimulation is a simple, safe, and minimally invasive technique with low morbidity and excellent results, which appear to be maintained for the first 6 years after the procedure. For patients who underwent the treatment, median Wexner incontinence score decreased significantly after a median follow-up of 24 (range, 3-72) months. Twelve percent were explanted. The infection rate was 1.6%.

Magnetic anal sphincter augmentation for the treatment of fecal incontinence: a preliminary report from a feasibility study.

BACKGROUND: Magnetic sphincter augmentation, a successful treatment of gastroesophageal reflux disease, has been applied to treat fecal incontinence. The purpose of this feasibility study was to understand the safety profile as well as the potential benefit of this new device when it is implanted in patients with fecal incontinence. METHODS: A magnetic anal sphincter device was surgically implanted in candidates with documented fecal incontinence of more than 2 episodes per week at 3 investigational centers in Europe and the United States following ethics/institutional review board approval. The magnetic anal sphincter device was placed around the anal canal via a single anterior incision. All data were collected prospectively. The primary outcome measure was the reduction of incontinent episodes based on a daily continence diary. RESULTS: To date 14 patients have been implanted with the device (all female; mean age, 62.8 y; range, 41-74 y) with a median follow-up of 6 months. There have been no intraoperative complications. Mean hospital stay was 3 days; range, 1 to 7 days. Adverse events were observed in 7 patients. Three patients are no longer implanted with a device; 2 devices were removed and one passed spontaneously following a separation at the suture connection. Five patients with 6-month follow-up demonstrated a mean reduction in the number of average weekly incontinence episodes from 7.2 to 0.7 (90.9%) and a mean reduction in Wexner Continence Score from 17.2 to 7.8 (54.7%). Compared with baseline, quality of life improved in all 4 domains of the fecal incontinence quality of life (FIQoL) scoring system. No patients have reported that their condition has worsened. Two patients at 1-year follow-up both reported perfect continence. CONCLUSION: This preliminary study describes the use of a new device to treat fecal incontinence. Compared with existing devices, implantation is simple and it requires no adjustments from the physician or patient once the device is implanted. Initial assessment with a small number of patients shows promising outcomes with a limited incidence of complications and good restoration of continence.

Long-term outcome and safety of transanal irrigation for constipation and fecal incontinence.

PURPOSE: This study evaluated long-term results of transanal irrigation for defecation disturbances. METHODS: Three hundred and forty-eight patients [248 women and 100 men; median age 52 years (range, 5-85)] suffering from constipation and fecal incontinence were introduced to transanal irrigation. Patients using transanal irrigation at follow-up received a mailed questionnaire describing bowel function and practical procedures. Results from patients not responding and patients no longer using transanal irrigation were drawn from hospital records and telephone interviews. Background variables were analysed using multivariate logistic regression. RESULTS: After a mean follow-up of 21 months (range, 1-116) 163 of 348 patients (47 percent) had a successful outcome from treatment with transanal irrigation. Success rates varied between patients with different underlying pathology: neurogenic bowel dysfunction, 67 of 107 (63 percent); anal insufficiency, 36 of 70 (51 percent); sequela to anorectal surgery, 14 of 48 (29 percent); idiopathic constipation, 27 of 79 (34 percent); and miscellaneous, 19 of 44 (43 percent). Factors correlating with positive outcome were neurogenic bowel dysfunction and anal insufficiency as underlying pathology, low rectal volume at urge to defecate, low maximal rectal capacity, and low anal squeeze pressure increment. Two nonfatal bowel perforations were found in approximately 110,000 irrigation procedures. CONCLUSIONS: Transanal irrigation is simple and safe for long-term treatment for defecation disturbances with greatest benefit in patients with neurogenic bowel dysfunction.

Rectal evacuation and antegrade colonic luminal transport by sacral anterior root stimulation in pigs.

PURPOSE: Electrical sacral anterior root stimulation with a selective anodal block may relieve difficulties with bowel evacuation by selective colorectal activation and anal sphincter suppression. This study compares rectal evacuation induced by anodal block with that induced by unselective stimulation. METHODS: The sacral anterior roots were stimulated with cuff electrodes in seven chloralose-anesthetized minipigs. Anodal block and unselective stimulation were applied in random order and compared by anorectal manometry and by the obtained colorectal evacuation. Evacuation was quantified scintigraphically after retrograde radioactive paste installation. RESULTS: Unselective stimulation evoked sphincter activation which obstructed rectal evacuation during the 30-second stimulation period, after which poststimulation evacuation occurred (mean, 13%; P < 0.05). Anodal block reduced the anal canal pressure by median 83% compared with unselective stimulation. With unrestrained evacuation, a different evacuation pattern (mean, 18%; P < 0.05) occurred within the first ten seconds of the stimulation period and evacuated volume was higher (P = 0.08). Colonic evacuation reached a mean of 17% with unselective stimulation and 11% with anodal block. CONCLUSION: Anodal block and unselective sacral root stimulation induce rectal evacuation and colonic luminal transport in pigs. However, anodal block may improve stimulation-induced defecation by enabling a near-physiologic defecation pattern.